title: AMPK regulates K(ATP) channel trafficking via PTEN inhibition in leptin-treated pancreatic β-cells.
abstract: Leptin regulates pancreatic β-cell excitability through AMP-activated protein kinase (AMPK)-mediated ATP-sensitive potassium (KATP) channel trafficking. However, the signaling components connecting AMPK to KATP channel trafficking are not identified. In this study, we discovered that AMPK inhibits phosphatase and tensin homologue (PTEN) via glycogen synthase kinase 3β (GSK3β) and this signaling pathway is crucial for KATP channel trafficking in leptin-treated pancreatic β-cells. Pharmacologic or genetic inhibition of AMPK or GSK3β, but not casein kinase 2 (CK2), impaired leptin-induced PTEN inactivation and thereby KATP channel trafficking. The PTEN mutant lacking both protein and lipid phosphatase activity is sufficient to induce KATP channel trafficking without leptin. These results present a novel signaling mechanism that underlies leptin regulation of KATP channel trafficking in pancreatic β-cells. Our findings assist in gaining a broader perspective on the peripheral action of leptin on pancreatic β-cell physiology and glucose homeostasis.
authors.affiliation: Cell Physiology Laboratory and Biomembrane Plasticity Research Center, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 110-799, Republic of Korea; Department of Physiology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 110-799, Republic of Korea.
authors.forename: Sun-Hyun
authors.initials: SH
authors.lastname: Park
authors.forename: Won-Kyung
authors.initials: WK
authors.lastname: Ho
authors.forename: Ju-Hong
authors.initials: JH
authors.lastname: Jeon
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D005947:Glucose / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006706:Homeostasis; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D054086:KATP Channels / Q000378:metabolism*; D020738:Leptin / Q000494:pharmacology / Q000502:physiology*; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis; D051381:Rats
chemical_list: D054086:KATP Channels; D020738:Leptin; D038362:Glycogen Synthase Kinase 3; D055372:AMP-Activated Protein Kinases; D051059:PTEN Phosphohydrolase; D005947:Glucose
keywords: AMP-activated protein kinase; AMPK; ATP-sensitive potassium channel; CK2; GSK3β; K(ATP) channel; Leptin; PTEN; Pancreatic β-cell; TSC2; casein kinase 2; glycogen synthase kinase 3β; mTORC1; mammalian target of rapamycin complex 1; phosphatase and tensin homologue; tuberous sclerosis 2